Reno-protective Effects of Coreopsis Tinctoria Flavonoids in db/db Mice Models Through the AGE/RAGE Pathway

Introduction. The study investigates the renal protective effects of flavonoids derived from Coreopsis tinctoria Nutt in type ۲ diabetes using db/db mice. Methods. With the db/m mice born in the same litter as the non-diabetic normal group, ۸-week-old db/db mice were divided into four groups: a diabetes model group, a low-dose (۰.۴ g/kg) flavonoids group, a high-dose (۱.۲ g/kg) flavonoids group, and a metformin positive control group. Mice were treated daily for ۸ weeks. Results. After ۸ weeks of continuous gavage feeding, the high-dose group of flavonoids significantly improved fasting blood glucose levels in ۱۶-week-old db/db mice, and both dosages of flavonoids reduced average daily water intake. The levels of serum creatinine (CRE) and BUN in db/db diabetic mice were significantly reduced by both high and low dosages of flavonoids, mitigating the loss of glomerular cells under hyperglycemic conditions, inhibiting glomerular hypertrophy and mesangial matrix hyperplasia, and demonstrating protective effects on renal function damage. The levels of AGEs in db/db mice kidneys were elevated compared to db/m mice, but significantly decreased with flavonoid treatment. Flavonoids also reduced RAGE protein expression and NF-κB activation. Additionally, both doses of flavonoids lowered MDA and IL-۱β levels, and enhanced antioxidant enzyme activities. Conclusions. The study concludes that flavonoids from Coreopsis tinctoria Nutt can inhibit the accumulation of AGEs and binding to RAGE in kidneys, improve oxidative stress and inflammation, and protect against renal damage induced by hyperglycemia. This suggests their potential of flavonoids from Coreopsis tinctoria Nutt as functional food and medicine for diabetic nephropatthy.Introduction. The study investigates the renal protective effects of flavonoids derived from Coreopsis tinctoria Nutt in type ۲ diabetes using db/db mice. Methods. With the db/m mice born in the same litter as the non-diabetic normal group, ۸-week-old db/db mice were divided into four groups: a diabetes model group, a low-dose (۰.۴ g/kg) flavonoids group, a high-dose (۱.۲ g/kg) flavonoids group, and a metformin positive control group. Mice were treated daily for ۸ weeks. Results. After ۸ weeks of continuous gavage feeding, the high-dose group of flavonoids significantly improved fasting blood glucose levels in ۱۶-week-old db/db mice, and both dosages of flavonoids reduced average daily water intake. The levels of serum creatinine (CRE) and BUN in db/db diabetic mice were significantly reduced by both high and low dosages of flavonoids, mitigating the loss of glomerular cells under hyperglycemic conditions, inhibiting glomerular hypertrophy and mesangial matrix hyperplasia, and demonstrating protective effects on renal function damage. The levels of AGEs in db/db mice kidneys were elevated compared to db/m mice, but significantly decreased with flavonoid treatment. Flavonoids also reduced RAGE protein expression and NF-κB activation. Additionally, both doses of flavonoids lowered MDA and IL-۱β levels, and enhanced antioxidant enzyme activities. Conclusions. The study concludes that flavonoids from Coreopsis tinctoria Nutt can inhibit the accumulation of AGEs and binding to RAGE in kidneys, improve oxidative stress and inflammation, and protect against renal damage induced by hyperglycemia. This suggests their potential of flavonoids from Coreopsis tinctoria Nutt as functional food and medicine for diabetic nephropatthy.

کلیدواژه ها:

Coreopsis Tinctoria ، flavonoids ، diabetic nephropathy ، advanced glycation end products ، receptor for AGE